Bioadhesion, in particular mucoadhesion, has been of interest for the development of controlled drug delivery systems to improve buccal, nasal and oral administration of drugs. The oral and nasal cavities, for example, form convenient and easily accessible sites for drug delivery. Systemic administration via the buccal route has several advantages over peroral delivery: pre-systemic metabolism in the gastrointestinal tract and hepatic first-pass elimination are avoided (Hoogstraate and Wertz, Pharmaceutical Science and Technology Today 1(7) (1996) pp. 309-316).
Carboxylated polymers, such as poly(acrylic acid) and crosslinked poly(acrylic acid), are known to be effective as mucoadhesives (hereinafter bioadhesive compositions). Various bioadhesive compositions comprising poly(acrylic acid) are described, e.g., in WO 98/22097; EP 410,696; U.S. Pat. No. 5,643,60; U.S. Pat. No. 4,915,948; U.S. Pat. No. 5,895,804 and U.S. Pat. No. 6,284,235.
The use of bioadhesive compositions comprising carboxylated polymers has, however, been limited owing to problems associated with mucosal irritation. While attempts to reduce the degree of irritation have included blending these polymers with other materials, including polysaccharides, efforts to produce non-irritating bioadhesive matrices have resulted in compositions having decreased bioadhesion, which limits the amount of drug that can be incorporated into the composition.
There remains a need for a bioadhesive composition having increased bioadhesive properties, decreased irritation, and the capacity for higher drug loading. The current invention addresses this need.